Psoriasis is a chronic inflammatory skin disease in which dendritic cells (DCs) play a pivotal role by inducing Th1/Th17 immune responses; however, the regulation of DC activation in psoriasis remains largely unknown. Previously we found that the level of soluble CD100 was increased in sera of psoriasis patients, and CD100 promoted the activation of inflammasome in keratinocytes. In the present study, CD100 knockout mice were utilized for generation of imiquimod (IMQ)-induced psoriatic dermatitis, with the result that skin inflammation in the early, but not late, phase of the psoriatic dermatitis was significantly exacerbated compared to that in wild-type controls. This was attributed mainly to the deficiency of CD100 in hematopoietic cells. Bone marrow-derived DCs, but not T cells or keratinocytes, from CD100 knockout mice produced significantly increased levels of IL-1β, IL-36, and IL-23 upon stimulation with IMQ in a plexin-B2-dependent manner. Moreover, the surface level of plexin-B2 on DCs of psoriasis patients was lower than that of healthy individuals, and CD100 attenuated IMQ-induced production of IL-1β and IL-36 from monocyte-derived DCs of psoriasis patients. Our results uncovered a negative regulatory mechanism for DCs activation in psoriasis, which was mediated via CD100-plexin-B2 in a cell type- and receptor-specific manner. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

中文翻译：

---

通过CD100-plexin-B2介导的牛皮癣中树突状细胞活化的负调控。

牛皮癣是一种慢性炎症性皮肤病，其中树突状细胞（DC）通过诱导Th1 / Th17免疫反应发挥关键作用。然而，牛皮癣中DC激活的调控仍然未知。以前我们发现牛皮癣患者血清中可溶性CD100的水平增加，而CD100促进角质形成细胞中炎性小体的活化。在本研究中，将CD100基因敲除小鼠用于生成咪喹莫特（IMQ）诱导的牛皮癣皮炎，其结果是，与野生型牛皮癣相比，牛皮癣皮炎的早期（而非晚期）炎症明显加剧。类型控件。这主要归因于造血细胞中CD100的缺乏。骨髓来源的DC，但不是T细胞或角质形成细胞，CD100基因敲除小鼠经IMQ刺激后，以plexin-B2依赖性方式产生的IL-1β，IL-36和IL-23水平显着增加。此外，牛皮癣患者DC上的plexin-B2的表面水平低于健康个体，并且CD100减弱了IMQ诱导的牛皮癣患者单核细胞衍生DC的IMQ诱导的IL-1β和IL-36的产生。我们的结果揭示了牛皮癣中DCs激活的负调控机制，该机制是通过CD100-plexin-B2以细胞类型和受体特异性方式介导的。©2020英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版 牛皮癣患者DC上plexin-B2的表面水平低于健康个体，CD100减弱IMQ诱导的牛皮癣患者单核细胞DC产生的IMQ诱导的IL-1β和IL-36的产生。我们的结果揭示了牛皮癣中DCs激活的负调控机制，该机制是通过CD100-plexin-B2以细胞类型和受体特异性方式介导的。©2020英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版 牛皮癣患者DC上plexin-B2的表面水平低于健康个体，CD100减弱IMQ诱导的牛皮癣患者单核细胞DC产生的IMQ诱导的IL-1β和IL-36的产生。我们的结果揭示了牛皮癣中DCs激活的负调控机制，该机制是通过CD100-plexin-B2以细胞类型和受体特异性方式介导的。©2020英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版